Metastatic renal cell carcinoma: recent advances in the targeted therapy era.

CONTEXT: The treatment of metastatic renal cell carcinoma (mRCC) has recently evolved from being predominantly cytokine based to being grounded in the use of targeted agents.
OBJECTIVE: To analyse current evidence on the medical management of mRCC. EVIDENCE ACQUISITION: The PubMed and Medline databases were searched for articles published as of 15 July 2009. Only articles published in English were considered. The search terms were metastatic renal cell cancer, targeted therapy, and immunotherapy. Proceedings from the 2000-2009 conferences of the American Society of Clinical Oncology, the American Urological Association, and the European Association of Urology were also searched for relevant abstracts. EVIDENCE SYNTHESIS: Sunitinib has recently emerged as a front-line standard of care in mRCC. Temsirolimus is considered a first-line therapy for patients with poor risk features. Bevacizumab/interferon is likely to be the next U.S. Food and Drug Administration-approved first-line treatment. The use of sorafenib has moved toward second-line and later therapy. Everolimus was the first agent to show clinical benefit post-tyrosine kinase inhibitor failure in a phase 3 study and is considered the standard of care in this setting. Temsirolimus provided benefit to patients with non-clear-cell histology. In preliminary results, a favourable risk-benefit ratio has been shown with pazopanib and axitinib as first- and second-line treatment. Until combination therapy is clearly shown to be superior to monotherapy, it should be used in the context of a clinical trial. Deciding which is the best sequence to use in mRCC patients remains up to the best judgement of the treating physician. Cytoreductive nephrectomy in the presence of metastatic disease is often indicated as part of an integrated management strategy.
CONCLUSIONS: Given considerable advances in understanding the biology of mRCC, several new drugs have recently been developed, offering an increasing number of treatment options. A treatment algorithm based on the best available evidence so far can be therefore postulated, though it continues to evolve as data from ongoing trials become available.